Regioselective metal-catalyzed hydrophosphinylation of alkynes: Synthesis of enantiopure α- or β-substituted vinylphosphane oxides

Article abstract of DOI:10.1002/ejoc.200900658

Palladium was found to catalyze regioselective Markovnikov addition of chiral enantiopure 1r-oxo-2c,5t-diphenyiphospholane (1) to terminal alkynes, whereas rhodium catalysis offers selectively the (E)-anti-Markovnikov adduct, This strategy offers rapid ac

Full text of DOI:10.1002/ejoc.200900658

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200900658
Regioselective Metal-Catalyzed Hydrophosphinylation of Alkynes: Synthesis of
Enantiopure α- or β-Substituted Vinylphosphane Oxides
Amélie Duraud,[a] Martial Toffano,*[a] and Jean-Claude Fiaud[a]
Keywords: Alkynes / Homogeneous catalysis / Phosphorus heterocycles / Regioselectivity
Palladium was found to catalyze regioselective Markovnikov
addition of chiral enantiopure 1r-oxo-2c,5t-diphenylphos-
pholane (1) to terminal alkynes, whereas rhodium catalysis
offers selectively the (E)-anti-Markovnikov adduct. This
strategy offers rapid access to chiral and enantiopure α- or β-
substituted-1-alkenylphospholanes.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
gands[11] or chiral transfer agents.[12] With this in mind, we
commenced our study by a strategy to produce chiral
enantiopure vinylphosphane by metal-catalyzed hydrophos-
phinylation of alkynes (Scheme 1).
Introduction
Homogeneous catalysis is an increasingly useful and ver-
satile alternative for the construction of C–P bonds. The
addition of a P–H bond to an unsaturated carbon–carbon
bond is, in terms of synthetic value and atom economy, a
very attractive process for the construction of various or-
ganophosphorus compounds.[1] Particularly, metal-cata-
lyzed addition of a P–H bond to alkynes results in the for-
mation of P–alkene bonds.[2] This strategy has shown its
potential in the synthesis of phosphanes,[3] phosphonates,[4]
phosphinates,[5,4d] H-phosphinates[6] and phosphane ox-
ides.[7] To the best of our knowledge, although appropriate
catalyst or protocols are developed to produce the desired
branched or linear α-β-unsaturated organophosphorus
compounds, there are only two examples of synthesis of
chiral enantioenriched vinylphosphane from hydrophos-
phination of alkynes. The first process is based on the stereo-
specific hydrophosphinylation of alkynes with P-chiral
menthylphosphinate.[8] This strategy is regioselective but
suffers from the use of a stoichiometric amount of menthyl
chiral auxiliary. The second route is a palladium-catalyzed
asymmetric hydrophosphination process with phosphane–
borane.[9] In this case, P-chirogenic vinylphosphane–borane
was obtained up to 42%ee.
Scheme 1. Metal-catalyzed hydrophosphinylation of terminal alk-
yne with 1.
This strategy is based on the metal-catalyzed reaction of
enantiopure 1r-oxo-2c,5t-diphenylphospholane (1) with
alkynes. Its offers some advantages: (i) Chiral enantiopure
substituted vinylphosphane oxides can be accessed rapidly.
(ii) The substrate possesses a nonstereogenic phosphorus
atom, which avoids problems of stereochemical integrity.
(iii) The chirality is provided by the phospholane moiety
and not by the alkyne substrate. (iv) Either the α- or the
β-substituted vinylic product can be obtained. Results of
palladium-catalyzed hydrophosphinylation of various alk-
ynes are collected in Table 1.
No reaction occurred in the absence of catalyst. Surpris-
ingly, no product was obtained in the case of Pd(OAc)2 and
the diphosphane dppe, despite the usual good activity of
this standard catalyst in hydrophosphinylation reactions.[7d]
No better activity was observed with Pd(dba)2 (Table 1, En-
tries 1 and 2). We found that hydrophosphinylation of
phenylacetylene proceeded with total conversion at 80 °C
to give vinylic phospholane oxide 2a when the catalyst sys-
tem used was composed of 5 mol-% of tetrakis(triphenyl-
phosphane)palladium complex (Table 1, Entry 3). Under
these conditions, only the α adduct was obtained, and no
trace of the β isomer was detected by NMR spectroscopic
analysis. This result indicates that the phosphorus attacks
the internal carbon atom of the alkyne with total regioselec-
Results and Discussion
In our group, we are interested in the preparation of or-
ganophosphorus compounds based on the chiral trans-2,5-
diphenylphospholane[10] moiety and their applications as li-
[a] Institut de Chimie Moléculaire et des Matériaux d’Orsay –
UMR 8182
Bat 420 – Université Paris Sud, 91405 Orsay Cedex, France
Fax: +33-1-69154680
E-mail: mtoffano@icmo.u-psud.fr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900658.
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Eur. J. Org. Chem. 2009, 4400–4403

Regioselective Metal-Catalyzed Hydrophosphinylation of Alkynes
Table 1. Palladium-catalyzed hydrophosphinylation of alkynes.[a]
Table 2. Rhodium-catalyzed hydrophosphinylation of alkynes.[a]
[a] An equimolar mixture of 1 and an alkyne (0.5 mmol) in toluene
(1 mL) in the presence of 6 mol-% of [Rh(cod)Cl]2 (80 °C, 15 h).
[b] Yields of α/β determined by 1H and 31P NMR spectroscopy.
The isolated yields of pure products for analysis after column
chromatography are reported in parentheses. [c] The α isomer was
[a] An equimolar mixture of 1 and an alkyne in toluene, in the
presence of 5 mol-% of Pd(PPh3)4 (80 °C, 15 h). [b] Yields of α/β
1
not detected by H and 31P NMR spectroscopy.
1
determined by H and 31P NMR spectroscopy. The isolated yields
of pure products for analysis after column chromatography are re-
ported in parentheses. [c] The β isomer was not detected by 1H and
31P NMR spectroscopy.
compounds like diphenylphosphinic acid [Ph2P(O)OH] but
in the presence of PdMe2L2 as catalyst.[7b] With this in
mind, we observed, by NMR spectroscopy, a trace amount
of trans-2,5-diphenylphospholanic acid (4) in the starting
material, resulting of the slow oxidation of 1 (Figure 1). To-
tal absence of phosphinic acid 4 in the substrate does not
modify the selectivity, but the Pd-catalyzed reaction appears
cleaner and proceeds with higher conversion. The presence
or absence of 4 in the Rh-catalyzed hydrophosphination re-
action did not alter the results.
tivity. The results are similar for other alkynes and products
2a–g were obtained with total conversion of starting mate-
rial (31P NMR).[13]
Conversely, rhodium-catalyzed hydrophosphinylation of
alkynes led preferentially to the formation of the β adduct
with total conversion of 1 (Table 2). The reaction is clean
and highly selective for (E)-alkenylphospholane oxide iso-
mer 3. However, Rh catalysis seems to be slightly less re-
gioselective than Pd catalysis for some alkynes.
Indeed, despite the absence of the α isomer for 4-butyn-
1-ol, 4-pentyn-1-ol and 1-octyne (Table 2, Entries 6, 7 and
8), a trace amount of the α adduct was detected for phenyl
and naphthylacetylene (Table 2, Entries 1 and 2). In some
cases, the β adducts were contaminated by their corre-
sponding α isomer, suggesting a decrease in the regioselec-
tivity of the reaction (Table 2, Entries 3–5).
Figure 1. Phospholanic acid 4.
Mixing two equivalents of 1 with [Rh(cod)Cl]2 in [D8]-
toluene gave immediately a complex showing a doublet at δ
1-Ethynylcyclohexene selectively reacted at the triple = 141 ppm (JRh,P = 170 Hz) in the 31P NMR spectrum,
bond under both palladium and rhodium catalysis. This corresponding probably to the formation of RhP2(cod)Cl
proves the inertness of the internal double bond (Table 1, complex A (Figure 2). No other signals are detected. The
Entry 6 and Table 2, Entry 4). The reason for the total presence of complex A is based on previous work.[11b,11c,14]
selectivity for the branched product under palladium cataly- Furthermore, we observed no signal in the range from 0 to
1
sis is not clear. Indeed, it was demonstrated by Tanaka that –30 ppm in the H NMR spectrum, corresponding to the
hydrophosphinylation reactions of terminal alkynes with [Rh]–H bond.[4a,7c,15] Monitoring the reaction with phenyl-
secondary phosphane oxides such as diphenylphosphane acetylene at 80 °C by NMR spectroscopy revealed the slow
oxide, H–P(O)Ph2, in the presence of Pd(PPh3)4 form linear disappearance of complex A and new signals over 3 h at
products as the major products.[7a] In contrast, the same 5.8–6.0 ppm, corresponding to the vinylic protons of com-
group demonstrated that it is possible to increase the for- pounds 3a. The presence of the product was confirmed by
mation of the α adduct or to switch completely the regiose- 31P NMR spectroscopy. In the case of palladium studies,
lectivity of this reaction in the presence of 5 mol-% of acidic no signal corresponding to the [Pd]–H bond was observed.
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A. Duraud, M. Toffano, J.-C. Fiaud
SHORT COMMUNICATION
Acknowledgments
We gratefully acknowledge financial support from the Ministère de
l’Enseignement Supérieur et de la Recherche.
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Figure 2. RhP2(cod)Cl complex A.
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described in Scheme 2 for the rhodium-catalyzed hydro-
phosphinylation reaction. Complexes A and B resulting
from coordination and oxidative addition of 1 to [Rh(cod)-
Cl]2, respectively, would be in equilibrium. Insertion of the
acetylenic substrate into the Rh–H bond of B would offer
vinylic complex C. The [Rh]–C bond being cleaved by a
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proton in the spectra when monitoring the reaction by
NMR spectroscopy.
3613.
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[13] The isolated yields of pure product are low despite the high
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Conclusions
The mechanism of the hydrophosphinylation of alkynes
by using chiral enantiopure phospholane oxide 1 is still not
clear. However, in most cases, the reactions are selective
particularly when catalyzed with a palladium complex. This
strategy is applicable to a variety of alkynes and offers rapid
access to chiral enantiopure α- or β-substituted vinylphos-
pholane.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data and copies of
[14] In solution, secondary phosphane oxides exist in equilibrium
between pentavalent (phosphane oxide form) and trivalent
1
the H, 13C and 31P NMR spectra.
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Eur. J. Org. Chem. 2009, 4400–4403

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Received: June 16, 2009
Published Online: July 31, 2009
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